IV tPA was approved in 1996 based in part on the NINDS rtPA stroke trial, a two-part RCT looking first at neurologic improvement at 24 hours, and then at the odds of a good outcome (complete or nearly complete neurologic recovery) at three months

Patients who get tPA have a higher rate of hemorrhage, but overall mortality is similar

Patients with lower stroke scales (NIHSS < 20) did better

The efficacy of tPA goes way down as time from onset of symptoms increases: OR for good outcome 2.11 for treatment within 90 minutes, vs 1.69 for 90-180 minutes

Somewhere between 1-5% of all patients get angioedema with tPA, associated with use of ACE-inhibitors as well as infarcts in the insular and frontal cortex

The evidence for the extended window is much weaker and the benefit is less. ECASS III showed a benefit from 3-4.5 hours in a more carefully selected population (52% of treatment arm had a mRS of 0-1, vs 45% of controls)

1/3 of patients not treated with tPA because their symptoms are mild or improving end up having a poor final outcome

Informed consent should be obtained given the risks associated with treatment, but in an emergency, with family not available, it’s okay to go ahead and give tPA, and the FDA is on board with this